54024-22-5

Basic information

• Product Name: Desogestrel
• Synonyms: (17α)-13-Ethyl-11-methylene-18，19-dinorpregn-4-en-20-yn-17-ol;(8S,9S,10R,13S,14S,17R)-13-Ethyl-17-ethynyl-11-methylidene-1,2,3,6,7,8,9,10,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-17-ol;(17R)-13-Ethyl-11-methylene-18,19-dinorpregn-4-en-20-yn-17-ol;(8S,9S,10R,13S,14S,17R)-13-ethyl-17-ethynyl-11-methylene-1,2,3,6,7,8,9,10,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-17-ol;Desogestrel (50 mg);(8S,9S,10R,13S,14S,17R)-13-ethyl-17-ethynyl-11-Methylene-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-ol;DESTODENE;Desogestrel for system suitability, European Pharmacopoeia (EP) Reference Standard
• CAS NO: 54024-22-5
• Molecular Formula: C₂₂H₃₀O
• Molecular Weight: 310.47
• EINECS: 258-929-4
• Product Categories: Steroid and Hormone;Hormone Drugs;Intermediates & Fine Chemicals;Pharmaceuticals;Steroids
• Mol File: 54024-22-5.mol

Chemical Properties

• Melting Point: 109-110°C
• Boiling Point: 390.62°C (rough estimate)
• Flash Point: 187.9 ºC
• Appearance: white to off-white crystalline powder
• Density: 1.0169 (rough estimate)
• Vapor Pressure: 3.92E-09mmHg at 25°C
• Refractive Index: 1.5100 (estimate)
• Storage Temp.: -20°C Freezer
• Solubility: Practically insoluble in water, very soluble in methanol, freely soluble in anhydrous ethanol and in methylene chloride.
• PKA: 13.07±0.40(Predicted)
• Merck: 14,2926
• CAS DataBase Reference: Desogestrel(CAS DataBase Reference)
• NIST Chemistry Reference: Desogestrel(54024-22-5)
• EPA Substance Registry System: Desogestrel(54024-22-5)

Safety Data

• Safety Statements: 24/25
• RIDADR: UN 3077 9 / PGIII
• WGK Germany: 3
• RTECS: JF7975000
• Hazardous Substances Data: 54024-22-5(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Desogestrel is used as a progestogen with low androgenic potency for the development of oral contraceptives. It is combined with an estrogen to create a birth control medication that inhibits ovulation and prevents fertilization.
Used in Treatment of Polycystic Ovary Syndrome (PCOS):
Desogestrel is used as a treatment option for polycystic ovary syndrome, a hormonal disorder that can cause irregular periods, acne, and excessive hair growth in women. It helps regulate hormonal imbalances and alleviates symptoms associated with PCOS.
Used in Research and Development:
Desogestrel is used as a research compound for studying its effects on P-glycoprotein activity, which is involved in multidrug resistance in cancer cells. This application aids in the development of new drugs and therapies targeting cancer treatment.

Originator

Dicromil,Organol ,W. Germany,1981

Manufacturing Process

A solution of 1.0 g of 11,11-methylene-18-methyl-delta4-estren-17-one in 33 ml tetrahydrofuran was added to a potassium-acetylide solution in tetrahydrofuran. After 2 hours of stirring at 0°C to 5°C the reaction mixture was acidified with 2N H2SO4and processed further.By a chromatographic treatment on silica gel and crystallization from pentane 0.7 g of 11,11-methylene-17α-ethynyl-18-methyl-δ4-estren-17β-ol with a melting point of 109°C to 110°C and an [α]D of +55°C (CHCl3) was obtained.

Therapeutic Function

Progestin

Clinical Use

Desogestrel also is a prodrug and is rapidly metabolized in the intestinal mucosa and on first pass through the liver to its active metabolite, etonogestrel (3-ketodesogestrel). Following oral administration, the relative bioavailability for desogestrel is approximately 84%. Desogestrel also exhibits high selectivity for the progesterone receptor and low and rogenic activity, and it does not diminish the beneficial effects of estrogen on the lipid profile.

InChI:InChI=1/C22H30O/c1-4-21-14-15(3)20-17-9-7-6-8-16(17)10-11-18(20)19(21)12-13-22(21,23)5-2/h2,8,17-20,23H,3-4,6-7,9-14H2,1H3/t17-,18-,19-,20+,21-,22-/m0/s1

Synthetic route

C24H38O2Si → desogestrel (54024-22-5)

Conditions	Yield
With hydrogenchloride In methanol; water Solvent; Reflux;	96.5%

lithium acetylide-ethylenediamine complex (1216963-74-4) + 11-methylene-18a-homo-estr-4-en-17-one (54024-21-4) → desogestrel (54024-22-5)

Conditions	Yield
In dimethyl sulfoxide at 20℃; for 21h;	89%

11-methylene-18a-homo-estr-4-en-17-one (54024-21-4) + trimethylsilylacetylene (1066-54-2) → desogestrel (54024-22-5)

Conditions	Yield
Stage #1: trimethylsilylacetylene With n-hexyllithium In tetrahydrofuran; hexane at -5℃; for 0.5h; Stage #2: 11-methylene-18a-homo-estr-4-en-17-one In tetrahydrofuran; hexane at 0 - 5℃; for 1h;	89%

11-methylene-18a-homo-estr-4-en-17-one (54024-21-4) + acetylene (74-86-2) → desogestrel (54024-22-5)

Conditions	Yield
With lithium; ethylenediamine In tetrahydrofuran at 25℃; for 2h; continuous flow of ethyne;	85%
Stage #1: acetylene With lithium In ethylenediamine at 20℃; for 2h; Peterson olefination; Stage #2: 11-methylene-18a-homo-estr-4-en-17-one In tetrahydrofuran at 20℃; for 2h; Further stages;	83%
Stage #1: acetylene With N,N,N,N,-tetramethylethylenediamine; lithium for 2h; Stage #2: 11-methylene-18a-homo-estr-4-en-17-one In tetrahydrofuran at 20℃; for 2h; Stage #3: With hydrogenchloride; water In tetrahydrofuran	83%

C24H32OS2 (116930-33-7) → desogestrel (54024-22-5)

Conditions	Yield
With sodium In tetrahydrofuran; ammonia at -4℃; for 1h;	58%

lithium acetylide-ethylenediamine complex (1216963-74-4) + 11-methylene-18a-homo-estr-4-en-17-one (54024-21-4) → desogestrel (54024-22-5) + 16β-OH desogestrel

Conditions	Yield
In tetrahydrofuran; ethylenediamine at 10 - 20℃; for 4h;	A 0.220 g B 0.060 g

(+)-(1S,3aS,7aS)-hexahydro-1-(tert-butyldimethylsiloxy)-7a-ethyl-5-indanone (220332-76-3) → desogestrel (54024-22-5)

Conditions

Yield

Multi-step reaction with 12 steps 1: 80 percent / NaH, MeOH / tetrahydrofuran; hexane / 1 h / Heating 2: 1.) NaH, 2.) n-BuLi 3: 1.) trifluoroacetic acid, 2.) K2CO3, MeOH / 1.) CH2Cl2, 23 deg C, 24 h, 2.) 23 deg C, 1 h 4: 73 percent / imidazole / dimethylformamide / 12 h / 50 °C 5: 95 percent / LiAlH4 / tetrahydrofuran / 2 h / 23 °C 6: 85 percent / DEAD, PPh3, o-NO2PhSO2NHNH2 / tetrahydrofuran / 14 h / -40 - 23 °C 7: liq. NH3, Li / ethanol; tetrahydrofuran / 1 h / -78 °C 8: 1 M aq. HCl, 48 percent aq. HF / tetrahydrofuran / 20 h / 23 °C 9: 100 percent / BF3*Et2O / methanol / 2 h / 23 °C 10: Li, liq. NH3 / tetrahydrofuran / 0.5 h / Heating 11: 99 percent / Dess-Martin periodinane / CH2Cl2 / 1 h / 23 °C 12: 1.) n-BuLi, 2.) Ce(III) chloride View Scheme

(+)-(1S,3aS,7aS)-3a,4,7,7a-tetrahydro-1-(tert-butyldimethylsiloxy)-6-carbomethoxy-7a-ethyl-5-hydroxyindane (220332-77-4) → desogestrel (54024-22-5)

Conditions

Yield

Multi-step reaction with 11 steps 1: 1.) NaH, 2.) n-BuLi 2: 1.) trifluoroacetic acid, 2.) K2CO3, MeOH / 1.) CH2Cl2, 23 deg C, 24 h, 2.) 23 deg C, 1 h 3: 73 percent / imidazole / dimethylformamide / 12 h / 50 °C 4: 95 percent / LiAlH4 / tetrahydrofuran / 2 h / 23 °C 5: 85 percent / DEAD, PPh3, o-NO2PhSO2NHNH2 / tetrahydrofuran / 14 h / -40 - 23 °C 6: liq. NH3, Li / ethanol; tetrahydrofuran / 1 h / -78 °C 7: 1 M aq. HCl, 48 percent aq. HF / tetrahydrofuran / 20 h / 23 °C 8: 100 percent / BF3*Et2O / methanol / 2 h / 23 °C 9: Li, liq. NH3 / tetrahydrofuran / 0.5 h / Heating 10: 99 percent / Dess-Martin periodinane / CH2Cl2 / 1 h / 23 °C 11: 1.) n-BuLi, 2.) Ce(III) chloride View Scheme

(+)-13β-ethyl-11-methylenegona-4-en-17β-ol (54024-20-3) → desogestrel (54024-22-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: 99 percent / Dess-Martin periodinane / CH2Cl2 / 1 h / 23 °C 2: 1.) n-BuLi, 2.) Ce(III) chloride View Scheme

(+)-13β-ethyl-17β-hydroxy-11-methylenegona-4-en-3-one (220332-82-1) → desogestrel (54024-22-5)

Conditions	Yield
Multi-step reaction with 4 steps 1: 100 percent / BF3*Et2O / methanol / 2 h / 23 °C 2: Li, liq. NH3 / tetrahydrofuran / 0.5 h / Heating 3: 99 percent / Dess-Martin periodinane / CH2Cl2 / 1 h / 23 °C 4: 1.) n-BuLi, 2.) Ce(III) chloride View Scheme

11-carbomethoxy-13-ethyl-3-methoxygona-1,3,5(10),9(11)-tetraen-17β-ol (220332-79-6) → desogestrel (54024-22-5)

Conditions

Yield

Multi-step reaction with 9 steps 1: 73 percent / imidazole / dimethylformamide / 12 h / 50 °C 2: 95 percent / LiAlH4 / tetrahydrofuran / 2 h / 23 °C 3: 85 percent / DEAD, PPh3, o-NO2PhSO2NHNH2 / tetrahydrofuran / 14 h / -40 - 23 °C 4: liq. NH3, Li / ethanol; tetrahydrofuran / 1 h / -78 °C 5: 1 M aq. HCl, 48 percent aq. HF / tetrahydrofuran / 20 h / 23 °C 6: 100 percent / BF3*Et2O / methanol / 2 h / 23 °C 7: Li, liq. NH3 / tetrahydrofuran / 0.5 h / Heating 8: 99 percent / Dess-Martin periodinane / CH2Cl2 / 1 h / 23 °C 9: 1.) n-BuLi, 2.) Ce(III) chloride View Scheme

(+)-13β-ethyl-3,3-ethylenedithio-11-methylenegona-4-en-17β-ol (54024-19-0) → desogestrel (54024-22-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: Li, liq. NH3 / tetrahydrofuran / 0.5 h / Heating 2: 99 percent / Dess-Martin periodinane / CH2Cl2 / 1 h / 23 °C 3: 1.) n-BuLi, 2.) Ce(III) chloride View Scheme

17β-(tert-butyldimethylsiloxy)-13-ethyl-11-methylene-3-methoxygona-1,3,5(10)-triene (161640-05-7) → desogestrel (54024-22-5)

Conditions	Yield
Multi-step reaction with 6 steps 1: liq. NH3, Li / ethanol; tetrahydrofuran / 1 h / -78 °C 2: 1 M aq. HCl, 48 percent aq. HF / tetrahydrofuran / 20 h / 23 °C 3: 100 percent / BF3*Et2O / methanol / 2 h / 23 °C 4: Li, liq. NH3 / tetrahydrofuran / 0.5 h / Heating 5: 99 percent / Dess-Martin periodinane / CH2Cl2 / 1 h / 23 °C 6: 1.) n-BuLi, 2.) Ce(III) chloride View Scheme

17β-(tert-butyldimethylsiloxy)-13-ethyl-11-(hydroxymethyl)-3-methoxygona-1,3,5(10),9(11)-tetraene (220332-81-0) → desogestrel (54024-22-5)

Conditions

Yield

Multi-step reaction with 7 steps 1: 85 percent / DEAD, PPh3, o-NO2PhSO2NHNH2 / tetrahydrofuran / 14 h / -40 - 23 °C 2: liq. NH3, Li / ethanol; tetrahydrofuran / 1 h / -78 °C 3: 1 M aq. HCl, 48 percent aq. HF / tetrahydrofuran / 20 h / 23 °C 4: 100 percent / BF3*Et2O / methanol / 2 h / 23 °C 5: Li, liq. NH3 / tetrahydrofuran / 0.5 h / Heating 6: 99 percent / Dess-Martin periodinane / CH2Cl2 / 1 h / 23 °C 7: 1.) n-BuLi, 2.) Ce(III) chloride View Scheme

(+)-(1S,3aS,4S,7aS)-3a,4,7,7a-tetrahydro-1-(tert-butyldimethylsiloxy)-6-carbomethoxy-7a-ethyl-5-hydroxy-4-(2-(3-methoxyphenyl)ethyl)indane (220332-78-5) → desogestrel (54024-22-5)

Conditions

Yield

Multi-step reaction with 10 steps 1: 1.) trifluoroacetic acid, 2.) K2CO3, MeOH / 1.) CH2Cl2, 23 deg C, 24 h, 2.) 23 deg C, 1 h 2: 73 percent / imidazole / dimethylformamide / 12 h / 50 °C 3: 95 percent / LiAlH4 / tetrahydrofuran / 2 h / 23 °C 4: 85 percent / DEAD, PPh3, o-NO2PhSO2NHNH2 / tetrahydrofuran / 14 h / -40 - 23 °C 5: liq. NH3, Li / ethanol; tetrahydrofuran / 1 h / -78 °C 6: 1 M aq. HCl, 48 percent aq. HF / tetrahydrofuran / 20 h / 23 °C 7: 100 percent / BF3*Et2O / methanol / 2 h / 23 °C 8: Li, liq. NH3 / tetrahydrofuran / 0.5 h / Heating 9: 99 percent / Dess-Martin periodinane / CH2Cl2 / 1 h / 23 °C 10: 1.) n-BuLi, 2.) Ce(III) chloride View Scheme

17β-(tert-butyldimethylsiloxy)-11-carbomethoxy-13-ethyl-3-methoxygona-1,3,5(10),9(11)-tetraene (220332-80-9) → desogestrel (54024-22-5)

Conditions

Yield

Multi-step reaction with 8 steps 1: 95 percent / LiAlH4 / tetrahydrofuran / 2 h / 23 °C 2: 85 percent / DEAD, PPh3, o-NO2PhSO2NHNH2 / tetrahydrofuran / 14 h / -40 - 23 °C 3: liq. NH3, Li / ethanol; tetrahydrofuran / 1 h / -78 °C 4: 1 M aq. HCl, 48 percent aq. HF / tetrahydrofuran / 20 h / 23 °C 5: 100 percent / BF3*Et2O / methanol / 2 h / 23 °C 6: Li, liq. NH3 / tetrahydrofuran / 0.5 h / Heating 7: 99 percent / Dess-Martin periodinane / CH2Cl2 / 1 h / 23 °C 8: 1.) n-BuLi, 2.) Ce(III) chloride View Scheme

tert-butyl-(13-ethyl-3-methoxy-11-methylene-2,6,7,8,9,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yloxy)-dimethyl-silane → desogestrel (54024-22-5)

Conditions	Yield
Multi-step reaction with 5 steps 1: 1 M aq. HCl, 48 percent aq. HF / tetrahydrofuran / 20 h / 23 °C 2: 100 percent / BF3*Et2O / methanol / 2 h / 23 °C 3: Li, liq. NH3 / tetrahydrofuran / 0.5 h / Heating 4: 99 percent / Dess-Martin periodinane / CH2Cl2 / 1 h / 23 °C 5: 1.) n-BuLi, 2.) Ce(III) chloride View Scheme

13β-ethyl-11-methylenegon-4-en-3,17-dione (54024-17-8) → desogestrel (54024-22-5)

Conditions	Yield
Multi-step reaction with 5 steps 1: 98 percent / BF3*Et2O / methanol / 2.5 h / 0 - 5 °C 2: 100 percent / NaBH4 / methanol / 2 h / Ambient temperature 3: 94 percent / Na, liq. NH3 / tetrahydrofuran / 0.5 h / -50 - -45 °C 4: 82 percent / Jones' reagent / acetone / 0.25 h / -15 - -10 °C 5: 72 percent / n-C4H9Br, Li / tetrahydrofuran; diethyl ether / 1.) -10 deg C, 2 h; -5 deg C, 3 h, 2.) -5 deg C, 3 h View Scheme
Multi-step reaction with 3 steps 1: 91 percent / BF3*Et2O / tetrahydrofuran / 2.75 h / Heating 2: t-BuOK / tetrahydrofuran / 2 h / -20 - -15 °C 3: 58 percent / Na / liquid ammonia; tetrahydrofuran / 1 h / -4 °C View Scheme
Multi-step reaction with 5 steps 1.1: hydrogenchloride / 1,2-dimethoxyethane; 1,4-dioxane / -10 °C 1.2: 3 h / -15 - -10 °C 1.3: 0.67 h 2.1: sodium tetrahydroborate; water / ethanol / 0 - 20 °C 3.1: zinc; acetic acid / water / 12 h / 20 °C 4.1: sodium carbonate / water; tetrahydrofuran; dichloromethane / 0.17 h / 20 °C 4.2: 20 °C 5.1: ethylenediamine; lithium / tetrahydrofuran / 5 h / 30 - 50 °C View Scheme

13-ethyl-11-methylenegon-4-ene-3,17-dione cyclic 3-(1,2-ethanediyl dithioacetal) (54024-18-9) → desogestrel (54024-22-5)

Conditions	Yield
Multi-step reaction with 4 steps 1: 100 percent / NaBH4 / methanol / 2 h / Ambient temperature 2: 94 percent / Na, liq. NH3 / tetrahydrofuran / 0.5 h / -50 - -45 °C 3: 82 percent / Jones' reagent / acetone / 0.25 h / -15 - -10 °C 4: 72 percent / n-C4H9Br, Li / tetrahydrofuran; diethyl ether / 1.) -10 deg C, 2 h; -5 deg C, 3 h, 2.) -5 deg C, 3 h View Scheme
Multi-step reaction with 2 steps 1: t-BuOK / tetrahydrofuran / 2 h / -20 - -15 °C 2: 58 percent / Na / liquid ammonia; tetrahydrofuran / 1 h / -4 °C View Scheme

13β-ethyl-11α-hydroxygon-5-ene-3,17-dione (53067-82-6) → desogestrel (54024-22-5)

Conditions

Yield

Multi-step reaction with 9 steps 1: 94 percent / Jones' reagent / acetone / 0.25 h / -15 - -10 °C 2: 79 percent / HC(OEt)3, p-TsOH*H2O / CH2Cl2 / 7 h / Heating 3: 88 percent / benzene; diethyl ether / 3 h / 10 - 15 °C 4: 74 percent / p-TsOH*H2O / formic acid / 7 h / 50 - 60 °C 5: 98 percent / BF3*Et2O / methanol / 2.5 h / 0 - 5 °C 6: 100 percent / NaBH4 / methanol / 2 h / Ambient temperature 7: 94 percent / Na, liq. NH3 / tetrahydrofuran / 0.5 h / -50 - -45 °C 8: 82 percent / Jones' reagent / acetone / 0.25 h / -15 - -10 °C 9: 72 percent / n-C4H9Br, Li / tetrahydrofuran; diethyl ether / 1.) -10 deg C, 2 h; -5 deg C, 3 h, 2.) -5 deg C, 3 h View Scheme

13β-ethyl-gona-5-ene-3,11,17-trione-3,17-diethylene ketal (196716-43-5) → desogestrel (54024-22-5)

Conditions

Yield

Multi-step reaction with 7 steps 1: 88 percent / benzene; diethyl ether / 3 h / 10 - 15 °C 2: 74 percent / p-TsOH*H2O / formic acid / 7 h / 50 - 60 °C 3: 98 percent / BF3*Et2O / methanol / 2.5 h / 0 - 5 °C 4: 100 percent / NaBH4 / methanol / 2 h / Ambient temperature 5: 94 percent / Na, liq. NH3 / tetrahydrofuran / 0.5 h / -50 - -45 °C 6: 82 percent / Jones' reagent / acetone / 0.25 h / -15 - -10 °C 7: 72 percent / n-C4H9Br, Li / tetrahydrofuran; diethyl ether / 1.) -10 deg C, 2 h; -5 deg C, 3 h, 2.) -5 deg C, 3 h View Scheme

18-methyl-estra-4-en-3,11,17-trione (100071-90-7) → desogestrel (54024-22-5)

Conditions

Yield

Multi-step reaction with 8 steps 1: 79 percent / HC(OEt)3, p-TsOH*H2O / CH2Cl2 / 7 h / Heating 2: 88 percent / benzene; diethyl ether / 3 h / 10 - 15 °C 3: 74 percent / p-TsOH*H2O / formic acid / 7 h / 50 - 60 °C 4: 98 percent / BF3*Et2O / methanol / 2.5 h / 0 - 5 °C 5: 100 percent / NaBH4 / methanol / 2 h / Ambient temperature 6: 94 percent / Na, liq. NH3 / tetrahydrofuran / 0.5 h / -50 - -45 °C 7: 82 percent / Jones' reagent / acetone / 0.25 h / -15 - -10 °C 8: 72 percent / n-C4H9Br, Li / tetrahydrofuran; diethyl ether / 1.) -10 deg C, 2 h; -5 deg C, 3 h, 2.) -5 deg C, 3 h View Scheme

D-13β-Ethyl-11-methylenegon-4-en-17α-ol (196716-46-8) → desogestrel (54024-22-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: 82 percent / Jones' reagent / acetone / 0.25 h / -15 - -10 °C 2: 72 percent / n-C4H9Br, Li / tetrahydrofuran; diethyl ether / 1.) -10 deg C, 2 h; -5 deg C, 3 h, 2.) -5 deg C, 3 h View Scheme

D-13β-Ethyl-3,3-ethylenedithio-11-methylenegon-4-ene-17α-ol (196716-45-7) → desogestrel (54024-22-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: 94 percent / Na, liq. NH3 / tetrahydrofuran / 0.5 h / -50 - -45 °C 2: 82 percent / Jones' reagent / acetone / 0.25 h / -15 - -10 °C 3: 72 percent / n-C4H9Br, Li / tetrahydrofuran; diethyl ether / 1.) -10 deg C, 2 h; -5 deg C, 3 h, 2.) -5 deg C, 3 h View Scheme

D-13β-Ethyl-11β-hydroxy-11α-methylgon-5-ene-3,11-dione-3,17-diethylene ketal (196716-44-6) → desogestrel (54024-22-5)

Conditions

Yield

Multi-step reaction with 6 steps 1: 74 percent / p-TsOH*H2O / formic acid / 7 h / 50 - 60 °C 2: 98 percent / BF3*Et2O / methanol / 2.5 h / 0 - 5 °C 3: 100 percent / NaBH4 / methanol / 2 h / Ambient temperature 4: 94 percent / Na, liq. NH3 / tetrahydrofuran / 0.5 h / -50 - -45 °C 5: 82 percent / Jones' reagent / acetone / 0.25 h / -15 - -10 °C 6: 72 percent / n-C4H9Br, Li / tetrahydrofuran; diethyl ether / 1.) -10 deg C, 2 h; -5 deg C, 3 h, 2.) -5 deg C, 3 h View Scheme

13-ethyl-gona-4-ene-11α,17β-diol (160683-92-1) → desogestrel (54024-22-5)

Conditions

Yield

Multi-step reaction with 5 steps 1: 85 percent / SO3 pyridine complex / triethylamine; dimethylsulfoxide / 3 h / Ambient temperature 2: 85 percent / triethylorthoformate, p-toluenesulfonic acid hydrate / 3 h / 40 °C 3: 85 percent / NaH / dimethylsulfoxide; toluene / 12 h / 80 °C / sonification 4: p-toluenesulfonic acid hydrate / acetone / 12 h / Ambient temperature 5: 85 percent / Li, ethylenediamine / tetrahydrofuran / 2 h / 25 °C / continuous flow of ethyne View Scheme

18a-homo-estr-4-ene-11,17-dione (160683-93-2) → desogestrel (54024-22-5)

Conditions	Yield
Multi-step reaction with 4 steps 1: 85 percent / triethylorthoformate, p-toluenesulfonic acid hydrate / 3 h / 40 °C 2: 85 percent / NaH / dimethylsulfoxide; toluene / 12 h / 80 °C / sonification 3: p-toluenesulfonic acid hydrate / acetone / 12 h / Ambient temperature 4: 85 percent / Li, ethylenediamine / tetrahydrofuran / 2 h / 25 °C / continuous flow of ethyne View Scheme
Multi-step reaction with 3 steps 1: n-butyllithium / tetrahydrofuran; hexane / 15 - 30 °C 2: tetrahydrofuran; hexane / Reflux 3: hydrogenchloride / methanol; water / Reflux View Scheme
Multi-step reaction with 2 steps 1.1: tetrahydrofuran / 1.5 h / 0 - 10 °C 1.2: 1.5 h / 25 °C 2.1: n-hexyllithium / tetrahydrofuran; hexane / 0.5 h / -5 °C 2.2: 1 h / 0 - 5 °C View Scheme

3-methoxy-18a-homo-estra-2,5(10)-diene-11α,17β-diol (160683-85-2) → desogestrel (54024-22-5)

Conditions

Yield

Multi-step reaction with 8 steps 1: 92 percent / HCl / acetone; H2O 2: boron trifluoride diethyl ether / methanol / 1 h / Ambient temperature 3: 87 percent / Li, ethylamine / tetrahydrofuran / 0.5 h / -35 - -30 °C 4: 85 percent / SO3 pyridine complex / triethylamine; dimethylsulfoxide / 3 h / Ambient temperature 5: 85 percent / triethylorthoformate, p-toluenesulfonic acid hydrate / 3 h / 40 °C 6: 85 percent / NaH / dimethylsulfoxide; toluene / 12 h / 80 °C / sonification 7: p-toluenesulfonic acid hydrate / acetone / 12 h / Ambient temperature 8: 85 percent / Li, ethylenediamine / tetrahydrofuran / 2 h / 25 °C / continuous flow of ethyne View Scheme

3,3-ethylenedithio-18a-homo-estr-4-ene-11α,17β-diol (160683-91-0) → desogestrel (54024-22-5)

Conditions

Yield

Multi-step reaction with 6 steps 1: 87 percent / Li, ethylamine / tetrahydrofuran / 0.5 h / -35 - -30 °C 2: 85 percent / SO3 pyridine complex / triethylamine; dimethylsulfoxide / 3 h / Ambient temperature 3: 85 percent / triethylorthoformate, p-toluenesulfonic acid hydrate / 3 h / 40 °C 4: 85 percent / NaH / dimethylsulfoxide; toluene / 12 h / 80 °C / sonification 5: p-toluenesulfonic acid hydrate / acetone / 12 h / Ambient temperature 6: 85 percent / Li, ethylenediamine / tetrahydrofuran / 2 h / 25 °C / continuous flow of ethyne View Scheme

11-methylene-17-<(2,2-dimethyl)propane-1,3-dioxy>-18a-homo-estr-4-ene (160683-95-4) → desogestrel (54024-22-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: p-toluenesulfonic acid hydrate / acetone / 12 h / Ambient temperature 2: 85 percent / Li, ethylenediamine / tetrahydrofuran / 2 h / 25 °C / continuous flow of ethyne View Scheme

carbon monoxide (201230-82-2) + 2-(2-(1-phenylethylidene)hydrazinyl)pyridine + desogestrel (54024-22-5) → 2-{(8S,9S,10R,13S,14S,17S)-13-ethyl-17-hydroxy-11-methylene-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl}-4H-pyrido[1,2-a]pyrimidin-4-one

Conditions	Yield
With dimanganese decacarbonyl In toluene at 100℃; under 760.051 Torr; for 16h; Schlenk technique; Sealed tube;	86%

Dimethylphenylsilane (766-77-8) + desogestrel (54024-22-5) → (8S,9S,10R,13S,14S,17S)-17-((dimethyl(phenyl)silyl)ethynyl)-13-ethyl-11-methylene-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-ol

Conditions	Yield
With potassium hydroxide In 1,2-dimethoxyethane at 45℃; for 48h;	60%

desogestrel (54024-22-5) + allyl bromide (106-95-6) → 17-O-allyldesogestrel

Conditions	Yield
Stage #1: desogestrel With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 1.5h; Inert atmosphere; Stage #2: allyl bromide In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; for 16h; Inert atmosphere;	58%

desogestrel (54024-22-5) → 17α-Bromethinyl-18-methyl-11-methylen-4-oestren-17β-ol (91781-33-8)

Conditions	Yield
With N-Bromosuccinimide; silver nitrate In acetone for 0.75h; Ambient temperature;	51%

acetic anhydride (108-24-7) + desogestrel (54024-22-5) → Acetic acid (8S,9S,10R,13S,14S,17R)-13-ethyl-17-ethynyl-11-methylene-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl ester (160683-96-5)

Conditions	Yield
With perchloric acid In toluene for 1h; Ambient temperature;

Upstream product

• 116930-33-7 C₂₄H₃₂OS₂ 
• 54024-21-4 11-methylene-18a-homo-estr-4-en-17-one 
• 74-86-2 acetylene 
• 1216963-74-4 lithium acetylide-ethylenediamine complex 
• 220332-77-4 (+)-(1S,3aS,7aS)-3a,4,7,7a-tetrahydro-1-(tert-butyldimethylsiloxy)-6-carbomethoxy-7a-ethyl-5-hydroxyindane 
• 220332-82-1 (+)-13β-ethyl-17β-hydroxy-11-methylenegona-4-en-3-one 
• 54024-19-0 (+)-13β-ethyl-3,3-ethylenedithio-11-methylenegona-4-en-17β-ol 
• 220332-81-0 17β-(tert-butyldimethylsiloxy)-13-ethyl-11-(hydroxymethyl)-3-methoxygona-1,3,5(10),9(11)-tetraene 
• 220332-78-5 (+)-(1S,3aS,4S,7aS)-3a,4,7,7a-tetrahydro-1-(tert-butyldimethylsiloxy)-6-carbomethoxy-7a-ethyl-5-hydroxy-4-(2-(3-methoxyphenyl)ethyl)indane 
• 220332-80-9 17β-(tert-butyldimethylsiloxy)-11-carbomethoxy-13-ethyl-3-methoxygona-1,3,5(10),9(11)-tetraene 
• 54024-17-8 13β-ethyl-11-methylenegon-4-en-3,17-dione 
• 54024-18-9 13-ethyl-11-methylenegon-4-ene-3,17-dione cyclic 3-(1,2-ethanediyl dithioacetal) 
• 53067-82-6 13β-ethyl-11α-hydroxygon-5-ene-3,17-dione 
• 100071-90-7 18-methyl-estra-4-en-3,11,17-trione 

Downstream Products

• 54048-10-1 etonogestrel 

Relevant articles and documents

Base promoted air oxidation of 13β-ethyl-11-methylenegon-4-en-17-one

The structure of 13-ethyl-11-methylene-18,19-dinor-17α-pregn-4-en-20-yn-16β,17-diol (3, 16β-OH desogestrel), a by-product obtained in the last step of the synthesis of desogestrel (1) by reaction of monolithium acetylide-ethylenediamine complex with 13β-e

PROCESS AND NEW INTERMEDIATES FOR THE PREPARATION OF 11-METHYLENE STEROIDS

The invention relates to a process for the preparation of 11 -methylene steroids through selective olefination of the ketone at position 11. The resulting products are useful intermediates in the preparation of several pharmaceutically active agents, such as Etonogestrel and Desogestrel.

Desogestrel preparation method and midbody compound

The invention relates to a novel steroidal compound and application of the novel steroidal compound in a desogestrel preparation process. The novel compound easy to separate is obtained through 17-bit selective ethynylation of 13beta-ethyl pregnane-4, 5-alkene-11, 17-diketone. When the compound is used for preparing desogestrel, simplicity and convenience in operation are achieved, and yield is high.

Intermediate used for synthesis of desogestrel, and preparation method and application thereof

The invention discloses an intermediate used for synthesis of desogestrel, and a preparation method and application thereof. The intermediate has a general chemical structural formula as described in the specification, wherein a substituting group R is selected from the group consisting of hydrogen, methyl or ethyl. The intermediate is prepared by subjecting a compound as shown in a formula 2 to selective protection reaction for a 3-carbonyl group by using dihydric alcohol, wherein the dihydric alcohol has a chemical structural formula as described in the specification, wherein R is selected from the group consisting of hydrogen, methyl or ethyl; and a reaction formula of the dihydric alcohol is described in the specification. The method for the synthesis of the desogestrel by employing the intermediate comprises a reaction route as described in the specification.

Desogestrel and its new process for preparation of the intermediate compounds

The invention relates to a preparation process for desogestrel and a novel intermediate compound thereof. In the prior art, 11-bit methylene is introduced through a wittig reaction in the preparation process of desogestrel, and a large quantity of environmental pollutants are produced in the reaction. In the preparation process for desogestrel and the novel intermediate compound thereof provided by the invention, the 11-bit methylene is introduced through an addition reaction, so that the problem of excessive discharge of pollutants is solved, reaction time is shortened, yield is increased, and industrial production is facilitated.

COMBINED SYNTHESIS ROUTE FOR ETONOGESTREL AND DESOGESTREL

The present invention relates to a synthesis route and to steroid derivatives of general formula VI and VII useful in the synthesis of desogestrel and etonogestrel.

TOTAL SYNTHESIS OF ENANTIOPURE DESOGESTREL

The present invention relates to a total synthesis of desogestrel and derivatives thereof, and to intermediate compounds of this synthesis.

Enantioselective total synthesis of the oral contraceptive desogestrel by a double heck reaction

A novel enantioselective total synthesis of the oral contraceptive desogestrel (2) is described, in which the tetracyclic steroid core is formed by a sequence of two consecutive Heck reactions. Conversion of the known enantiopure diketone 7 led to the chiral bicycle 6 which was used for a diastereoselective intermolecular Heck reaction with vinyliodide 5 to give 15. In the following intramolecular Heck reaction, the tetracyclic ring system was formed to give 4, from which the synthesis of desogestrel (2) was furnished.

PROCESS AND NEW INTERMEDIATES FOR THE PREPARATION OF STEROIDS WITH A PROGESTOGEN ACTIVITY

The present invention relates to a new process of synthesis and to some new intermediates for the preparation of steroids with progestogen activity, more particularly, for the preparation of Desogestrel of formula (I). Said process is characterized by the regioselective reduction of the compound of formula (II) to give the intermediate of formula (III).